Substituted pyrimidoindoles and diazepinoindoles useful as hypoglycaemics

Abstract

Compounds of formula (I) ##STR1## and their pharmaceutically acceptable acid addition salts, wherein R represents lower alkyl or a mono- or bicyclic aryl or heteroaryl radical, R 1 and R 2 which may be the same or different each represent hydrogen, hydroxyl, lower alkyl, lower alkoxy, halo(lower)alkyl, halogen, amino or mono- or di(lower)alkylamino, X represents--CH 2 CR 3 R 4 CH 2 --or --(CH 2 ) 4 --where R 3 and R 4 each independently represent hydrogen or lower alkyl or R 3 and R 4 together with the carbon atom to which they are attached represent a 5, 6 or 7 membered carbocyclic ring and R 5 represents acyl and R 6 represents hydrogen or R 5 and R 6 each independently represent hydrogen or lower alkyl, are useful as hypoglycaemics.

I claim: 
     
       1. A compound of the formula: ##STR5## in which R is alkyl of 1 to 6 carbon atoms or substituted or unsubstituted phenyl, in which the substituents are hydroxyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, halo, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms; R 1  and R 2  are, independently, hydrogen, hydroxyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, halo, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms;   X is --CH 2  --CR 3  R 4  --CH 2  -- or --(CH 2 ) 4  -- where R 3  and R 4 , independently, are hydrogen or alkyl of 1 to 6 carbon atoms, and, when taken together with the carbon atom to which they are attached, R 3  and R 4  complete a cyclopentane, cyclohexane or cycloheptane ring;   R 5  and R 6 , independently, are hydrogen or alkyl of 1 to 6 carbon atoms, or R 6  is hydrogen and R 5  is alkylcarbonyl, where the alkyl group is of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof.     
     
     
       2. A compound of claim 1 in which R is phenyl or phenyl substituted by one or more halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 atoms or haloalkyl substituent of 1 to 4 carbon atoms. 
     
     
       3. A compound of claim 1 in which X is --CH 2  CR 3  R 4  CH 2  -- wherein R 3  and R 4  are hydrogen or alkyl of 1 to 4 carbon atoms or when taken together with the carbon atom to which they are attached, they complete a cyclopentane, cyclohexane or cycloheptane ring. 
     
     
       4. A compound of claim 1 in which R 5  is alkanoyl of 2 to 7 carbon atoms and R 6  is hydrogen. 
     
     
       5. A compound according to claim 1 which is 10-Amino-2,3,4,10-tetrahydro-3,3-dimethyl-10-phenylpyrimido[1,2-a]indole or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       6. A compound of claim 1 which is 10-acetamido-10-(3-chlorophenyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       7. A compound of claim 1 which is 10-amino-10-(3-chlorophenyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       8. A compound of claim 1 which is 10-acetamido-2,3,4,10-tetrahydro-10-phenylpyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       9. A compound of claim 1 which is 10-amino-10-phenyl-2,3,4,10-tetrahydropyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       10. A compound of claim 1 which is 10-acetamido-2,3,4,10-tetrahydro-3,3-dimethyl-10-phenylpyrimido[1,2-]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       11. A compound of claim 1 which is 10-acetamido-2,3,4,10-tetrahydro-10-methylpyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       12. A compound of claim 1 which is 10'-acetamido-2',3',4',10'-tetrahydro-10'-phenylspiro[cyclohexane-1,3'-pyrimido[1,2a]indole], or a pharmaceutically acceptable salt thereof. 
     
     
       13. A compound of claim 1 which is 11-acetamido-2,3,4,5-tetrahydro-11-phenyl-11H-[1,3]diazepino[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       14. A compound of claim 1 which is 10'-acetamido-2',3',4',10-tetrahydro-10'-phenylspiro[cyclopentane-1,3'-pyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       15. A compound of claim 1 which is 10-butanamido-2,3,4,10-tetrahydro-3,3-dimethyl-10-phenylpyrimido[1,2-a]indole, or a pharmaceutically acceptable salt thereof. 
     
     
       16. A method of treating diabetes which comprises administering to a mammal in need thereof, a hypoglycemically effective amount of a compound of the formula: ##STR6## in which R is alkyl of 1 to 6 carbon atoms, or substituted or unsubstituted phenyl, in which the substituents are hydroxyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, halo, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms; R 1  and R 2  are, independently, hydrogen, hydroxyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, halo, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms;   X is --CH 2  --CR 3  R 4  --CH 2  -- or --(CH 2 ) 4  -- where R 3  and R 4 , independently, are hydrogen or alkyl of 1 to 6 carbon atoms, and, when taken together with the carbon atom to which they are attached, R 3  and R 4  complete a cyclopentane, cyclohexane or cycloheptane ring;   R 5  and R 6 , independently, are hydrogen or alkyl of 1 to 6 carbon atoms, or R 6  is hydrogen and R 5  is alkylcarbonyl, where the alkyl group is of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof.